crossing96/oncoscreening huggingface dataset:
Effect of small interfering RNA targeting survivin gene on biological behaviour of bladder cancer.	BACKGROUND: Bladder cancer is the most common type of urinary system tumours. It is frequently associated with genetic mutations that deregulate the cell cycle and render these tumours resistant to apoptosis. Survivin, a newly discovered member inhibitor of apoptosis protein (IAP) family in several human cancers, by inducing cell proliferation and inhibiting apoptosis is frequently activated in bladder cancer. We studied the influence of small interfering RNA (siRNA) targeting survivin on the biological behaviour of bladder cancer cells. METHODS: A double strand survivin target sequence specific siRNA was designed and synthesized. After transfection of bladder cancer cell line T24 by siRNA/liposome complex with increasing concentrations (50200 nmol/L), the transfectant cells were intratumourally injected at different doses (5 microg or 50 microg). The effects were measured in vitro and in vivo. RESULTS: The selected siRNA efficiently down-regulated survivin mRNA expression in a dose and time dependent manner. The maximal effect was achieved at the concentration of 100 nmol/L, at which survivin expression level was down-regulated by 75.91%. The inhibition rate of cell growth was 55.29% (P < 0.01) and the markedly increased apoptotic rate was 45.70% (P < 0.01). In vivo intratumoural injection of 50 microg siRNA-survivin could notably prevent the growth of bladder cancer (P < 0.01) in xenografted animals. CONCLUSION: The application of siRNA-survivin could markedly inhibit survivin expression in bladder cancer cell line by inducing apoptosis and inhibiting the growth of the tumour. It may become a new gene therapy tool for bladder cancer.	bladder
Ectopic adrenocorticotropic hormone syndrome in a case of small cell carcinoma of the bladder manifesting as severe muscle weakness.	Ectopic adrenocorticotropic hormone syndrome is a paraneoplastic syndrome associated with small cell carcinoma. However, ectopic adrenocorticotropic hormone syndrome is rare in association with small cell carcinoma of the bladder. We report what we believe to be the first case of ectopic adrenocorticotropic hormone syndrome associated with small cell carcinoma of the bladder that manifested as severe muscle weakness due to hypokalemia. An early diagnosis and aggressive potassium replacement is essential for retaining muscle strength. The patient died of pneumonia less than 2 months after the diagnosis. Severe immunosuppression by excess cortisol production was suspected. Control of cortisol levels before chemotherapy might be beneficial in preventing infective complications.	bladder
Evaluation of the vascular endothelial growth factor (VEGF)-C role in urothelial carcinomas of the bladder.	BACKGROUND: Vascular endothelial growth factor-C (VEGF-C) has been associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis and was reported to have an anti-apoptotic and proliferative role. MATERIALS AND METHODS: An immunohistochemical study was applied to 123 specimens of bladder urothelial carcinoma (BUC) to detect VEGF-C and investigate its clinicopathological and prognostic value. VEGF-C-immunostained BUC specimens (123) were statistically correlated with histological grade and stage, patient overall survival and immuno-expression of Ki-67 and bax proteins. RESULTS: VEGF-C immunopositivity (27/123 BUCs, 22.0%) was inversely correlated with tumor stage and bax immunoexpression (p = 0.007 and p = 0.032, respectively). VEGF-C-positive BUCs tended to have better prognosis (univariate analysis). CONCLUSION: VEGF-C might be associated with an anti-apoptotic phenotype. Our controversial results regarding patient survival suggest that the role of VEGF-C in BUC progression and prognosis remains to be clarified.	bladder
Inhibition of the epidermal growth factor receptor in bladder cancer cells treated with the DNA-damaging drug etoposide markedly increases apoptosis.	OBJECTIVE: To investigate the effect of the epidermal growth factor receptor (EGFR) on the induction of apoptosis by the chemotherapeutic agent etoposide (VP16), and to examine the effect of combining VP16 with gefitinib to see if the cell-survival mechanism can be prevented. MATERIALS AND METHODS: The bladder cancer cell lines RT4 and T24, representing low- and high-malignancy grades respectively, were treated with VP16 (10 or 50 microM) and the level of apoptosis determined using a commercial kit. EGFR receptor activity was determined by western blotting using antibodies against phosphorylated EGFR. The EGFR was either activated by heparin-binding (HB)-EGF (1 nM) or inhibited with the specific EGFR inhibitor gefitinib (1 or 5 microM). The pan-caspase inhibitor Z-VAD (30 microM) was used to test the involvement of caspase activity. RESULTS: Treatment of T24 bladder cancer cells with VP16 (50 microM) for 48 h induced phosphorylation of the EGFR and activation of the EGFR prevented the apoptosis induced by VP16. Thus, treatment of T24 cells with 50 microM VP16 for 48 h resulted in 19% apoptosis. However, activation of the EGFR with HB-EGF (1 nM) with VP16 (50 microM) significantly reduced the level of apoptosis by 25% (P < 0.05) showing that activating the EGFR has a cell-survival function. Inhibiting the EGFR with gefitinib (5 microM) blocked the VP16-induced activation of the EGFR. Combined treatment with gefitinib and VP16 resulted in 45% apoptotic cells, i.e. more than double the percentage of apoptotic cells with VP16 alone. This was found in both T24 and RT4 cells. Gefitinib used alone (1 and 5 microM) generated no apoptosis in the cells. Treatment of T24 cells with Z-VAD showed that apoptosis induced by both VP16 alone and VP16 with gefitinib was caspase-mediated. CONCLUSION: These results suggest that activation of the EGFR induced a cell-survival function when bladder cancer cells were treated with the DNA-damaging drug VP16, and that combined treatment with VP16 and the EGFR inhibitor gefitinib might improve the efficacy of treatment.	bladder
[Case of multiple thin-walled cavitary pulmonary metastasis from bladder cancer].	A 71-year-old man was admitted to the urological section of our hospital because of hematuria. Cystoscopy revealed a bladder tumor. Transurethral resection of the bladder tumor (TUR-Bt) was performed. This tumor was diagnosed pathologically as bladder cancer (transitional cell carcinoma pT2). His chest computed tomogram showed multiple thin-walled cavitary nodules in both lungs. The pathological images of the specimen that was resected by video assisted thoracic surgery (VATS) showed transitional cell carcinoma. A diagnosis of pulmonary metastasis from bladder cancer was made. This is a rare case.	bladder
[Determination of grade of urothelial carcinoma according to WHO 2004 classification].	Several classifications of transitional/urothelial cell tumors have been proposed during last few years in order to standardize nomenclature, and criteria for grading and invasion. They also aimed to avoid the term cancer for neoplasms that very rarely invade, recur, and/or cause death of the patient. As a result of these efforts a new WHO classification emerged in the year 2004. Instead of the term transitional, the use of urothelial neoplasms was recommended. In the group of noninvasive urothelial neoplasms, a new category of tumor of low malignant potential was added. Three-tier grading of papillary noninvasive tumor was substituted by low and high-grade category. Criteria for the grades are cited in the classification but are somewhat imprecise and difficult to apply. On the basis of the data from the literature and our own experience, in the transitional period we recommend the use of WHO 1973 simultaneously with the new one. Problems of the identification of lamina propria invasion are still not solved, and therefore the use of additional histochemical and immunohistochemical methods should be recommended in difficult cases.	bladder
A chemosensitivity test for superficial bladder cancer based on three-dimensional culture of tumour spheroids.	OBJECTIVES: Three-dimensional (3D) spheroids are a good model for studying in vitro chemosensitivity because they reproduce unicellular and multicellular mechanisms of drug resistance. We aimed to develop a chemosensitivity test for intravesical drugs and to also verify the effects of verapamil (VPM) and ciprofloxacin (CIPRO). METHODS: Cold cup biopsies from 40 superficial bladder tumours were taken, fragmented, and left in culture. 3D-spheroids were obtained and transferred into a 24 multiwell dish containing (1) wells 1-3: 1 mg/ml epirubicin (EPI); (2) 4-6: 1 mg/ml EPI+0.5 mg/ml VPM; (3) 7-9: 1 mg/ml adriamycin (ADR); (4) 10-12: 1 mg/ml thiotepa (THIO); (5) 13-15: 1 mg/ml mitomycin C (MMC); (6) 16-18: 1mg/ml EPI+0.2 mg/ml CIPRO; (7) 19-21: 0.2 mg/ml CIPRO; (8) 22-24: controls. Sensitivity was calculated by using the trypan blue assay. RESULTS: Evaluability of clinically relevant tests (G1-G2 lesions) was 84% (21 of 25 patients). MMC was the best agent (p<0.001) with mean sensitivity being 50%, followed by THIO (37%), EPI (7%), and ADR (3%). We found no significant difference (p=0.370) between CIPRO and the control, or between EPI+CIPRO and EPI alone (p=0.550). VPM markedly enhanced sensitivity to EPI compared with EPI alone (97% vs. 7%, p<0.001). CONCLUSIONS: Our assay allows determining sensitivity to several drugs in superficial bladder tumours. It might be used in clinical practice to select the best drug for each patient. It also has experimental utility in investigating the effect of new drugs or combinations. VPM reverted resistance to EPI. CIPRO showed no effect on bladder tumour spheroids.	bladder
Urothelial carcinoma (clear cell variant) diagnosed with useful immunohistochemistry stain.	The case is reported of urothelial carcinoma (clear cell variant) that was diagnosed with useful immunohistochemistry stain. A 70-year-old man, who had undergone left radical nephrectomy for renal cell carcinoma in August 2003 and partial lobectomy for pulmonary metastasis in May 2005, complained of hematuria in June 2005. On evaluation, a papillary pedunculated tumor was detected in the left wall of the urinary bladder. A transurethral resection of the bladder tumor (TUR-Bt) was performed in July 2005. The pathological diagnosis was difficult due to diffuse clear cell appearance. Immunohistochemistry stain showed urothelial carcinoma, not metastasis of the renal cell carcinoma. Finally it was diagnosed as urothelial carcinoma clear cell variant. Urothelial carcinoma has many variants that show a variety of appearances and characteristics. These should be well known before medical therapy is initiated.	bladder
Examination of a CpG island methylator phenotype and implications of methylation profiles in solid tumors.	The CpG island methylator phenotype (CIMP), thoroughly described in colorectal cancer and to a lesser extent in other solid tumors, is important in understanding epigenetics in carcinogenesis and may be clinically useful for classification of neoplastic disease. Therefore, we investigated whether this putative phenotype exists in exposure-related solid tumors, where somatic gene alterations and enhanced clonal growth are selected for by carcinogens, and examined the ability of methylation profiles to classify malignant disease. We studied promoter hypermethylation of 16 tumor suppressor genes and 3 MINT loci (acknowledged classifiers of CIMP) in 344 bladder cancers, 346 head and neck squamous cell carcinomas (HNSCC), 146 non-small-cell lung cancer (NSCLC), and 71 malignant pleural mesotheliomas (MPM). We employed rigorous statistical methods to examine the distribution of promoter methylation and the usefulness of these profiles for disease classification. In bladder cancer, HNSCC, and NSCLC, there was a significant correlation (P < 0.0001) between methylation of the three MINT loci and methylation index, although the distribution of methylated loci varied significantly across these disease. Although there was a significant (P < 0.001) association between gene methylation profile and disease, rates of misclassification of each disease by their methylation profile ranged from 28% to 32%, depending on the classification scheme used. These data suggest that a form of CIMP exists in these solid tumors, although its etiology remains elusive. Whereas the gene profiles of hypermethylation among examined loci could not unequivocally distinguish disease type, the existence of CIMP and the relative preponderance of hypermethylation in these cancers suggest that methylation analysis may be clinically useful as a targeted screening tool.	bladder
[Stage pT0 bladder tumors after radical cystectomy: a review of our series].	OBJECTIVES: To evaluate the data of progression and survival in 43 patients who underwent cystectomy with stage pT0 according to classification TNM-2002. MATERIALS AND METHODS: between 1988 and 2003 in our center had realized 420 cystectomies, 43 patients (10.2%) had not tumor in the cystectomy specimen. RESULTS: In these 43 cases the initial clinical stage (in the transuretral resection of bladder) was T1 in 10 cases (23,3 %), T2 in 31 cases (72%) and T3 in 2 cases. As far as the degree 24 patients presented G2 (55.8%) and 19 (44.2%) were G3. Median time from the transuretral resection to the cistectomy was of 44 days at a median follow-up of 89.3 months. Progression-free survival in the 43 patients was of 180,6 months, but during the follow-up it appeared progression in 7 patients, with disease free survival at 36 months (3-126), since the date of the cistectomia. During the follow up, 5 patients died. When we analyzed the cancer-specific survival according to tumor stage, for the T2 with an average cancer-specific survival is of 180 months, decreasing to 35 months considerably for T3. Similar it happens with the degree of differentiation, significantly diminishing as it advances the degree, with an average of cancer-specific survival for the G3 at 122.6 months. In the same way it happens with pathological positive lymph nodes in the radical cistectomy, with a cancer-specific survival of 188 months when it is N0 and of 54 months if the adenopathy was positive (N+). CONCLUSION: In our experiencie urothelial carcinoma pT0 present a prolonged free period of disease (medium of 180 months). The associated factors of risk to a smaller free period of disease are high degree of differentiation (G3, 116 months), the infiltration of deep layers in the transuretral resection (T3, 32 months) and the ganglionary affectation (pN+ 45 months).	bladder
Metastasis of squamous cell carcinoma of the bladder to the heart: case report and review of the literature.	A 79-year-old woman with no previous history of genitourinary disease presented to an outside urologist with gross hematuria and irritative voiding symptoms. Cystoscopy revealed a papillary bladder mass thought initially to represent urothelial carcinoma of the bladder with squamous features. The patient presented to our hospital 6 months later with dyspnea and edema. Computed tomography of the chest revealed a cardiac mass, and endomyocardial biopsy revealed metastatic squamous cell carcinoma. A review of the patient's pathology report confirmed the very rare diagnosis of metastatic squamous cell carcinoma of the bladder to the heart.	bladder
Collaboration of RON and epidermal growth factor receptor in human bladder carcinogenesis.	PURPOSE: Collaboration of heterologous receptor tyrosine kinases has emerged as an important paradigm in tumor progression. We recently proved that RON has an important role in human bladder carcinogenesis. Since epidermal growth factor receptor has been suggested to cross-talk with RON, we examined the significance of epidermal growth factor receptor in modulating RON associated tumorigenesis. MATERIALS AND METHODS: The biological significance of collaboration between RON and epidermal growth factor receptor was examined in the TSGH8301, J82 and JR bladder cancer cell lines with different expression status. Immunoprecipitation and immunoblotting assays were done to investigate the interaction of RON with epidermal growth factor receptor in relation to epidermal growth factor receptor kinase inhibitor treatment. Time lapse wound healing monitoring and Transwelltrade mark assay were used for cell migration analysis and the effect on cell transformation was analyzed with foci formation assay. Finally, a bladder cancer cohort of 78 patients was studied for clinical significance by immunohistochemistry. RESULTS: Epidermal growth factor receptor was directly associated with RON, irrespective of ligand stimulation. The siRNA experiment and epidermal growth factor receptor kinase inhibitors efficiently inhibited RON related biological effects, including mitogenesis, migration, anti-apoptosis and neoplastic transformation. Co-expression of RON/epidermal growth factor receptor was found in 26 of 78 patients (33.3%) with bladder cancer. It was significantly associated with tumor invasion (p < 0.05), the risk of local recurrence (p = 0.0003) and decreased patient survival (p = 0.04). Important indicators for patient survival were co-expression of RON and epidermal growth factor receptor (p = 0.001) and tumor staging (p = 0.05). CONCLUSIONS: Cross-talk between epidermal growth factor receptor and RON exists in vivo. Thus, it should be considered in treatment planning for patients with bladder cancer.	bladder
Chemotherapy practices and perspectives in invasive bladder cancer.	Bladder cancer is the fifth most common cancer in adult patients. Two-thirds of patients have superficial tumors and their treatment is conservative. Nevertheless, 30% of superficial tumors become infiltrative and represent a third of tumors at initial diagnosis. Overall mortality from bladder cancer is 30%. Important molecular events may explain the carcinogenesis and evolution of these tumors. Infiltrating bladder cancers are currently treated by radical cystectomy. Neoadjuvant chemotherapy has demonstrated a positive impact on patients' outcomes before cystectomy. Adjuvant chemotherapy after cystectomy is currently being studied in an international randomized trial. Patients with advanced disease are treated by chemotherapy with palliative intentions. Two regimens are standard: the combination of methotrexate, vinblastine, adriamycin and cisplatin, and the combination of gemcitabine and cisplatin. The addition of paclitaxel to the latter regimen is the subject of ongoing study. Only a few patients have long-term nonevolutive disease. Research must be focused on the combination of chemotherapy and targeted drugs directed through gene methylation, cytokine-receptor activation and signaling pathways.	bladder
The p53 pathway and outcome among patients with T1G3 bladder tumors.	PURPOSE: The aim was to analyze Tp53 and HDM2 in T1G3 bladder tumors and to determine the prognostic value of their alterations. EXPERIMENTAL DESIGN: Tumors (n = 119) were extracted from a prospective study of 1,356 bladder cancers. Tp53 mutations (exons 4-9) were assessed by sequencing of PCR products. HDM2 dose was assessed by quantitative PCR. p53, HDM2, and the products of p53 target genes were analyzed by immunohistochemistry. Cases were distributed in three categories. The association with prognosis was determined using Kaplan-Meier and Cox analyses. RESULTS: Eighty-five percent of tumors harbored alterations in Tp53 or HDM2. In group 1 (n = 77), 69 tumors had inactivating Tp53 mutations (58%), and 8 had HDM2 gains (7%). Group 2 (n = 24) comprised tumors overexpressing p53 in the absence of mutations (20%). Group 3 tumors (n = 18) had no alterations. HDM2 gains were associated to HDM2 overexpression and to wild-type Tp53. Expression of type 1 insulin-like growth factor receptor, 14-3-3 sigma, and cyclooxygenase-2 was similar in groups 1 and 2 and significantly different from group 3. Survivin was expressed in the majority of tumors regardless of p53 pathway status. Taking group 3 as reference, the hazard ratios (HR) for recurrence, progression, and death were not significantly different in the other patient groups. HRs for recurrence were 1.13 for group 1 [95% confidence interval (95% CI), 0.25-5.03] and 1.40 for group 2 (95% CI, 0.27-7.20). HRs for progression were 0.50 for group 1 (95% CI, 0.18-1.40) and 0.25 for group 2 (95% CI, 0.05-1.29). CONCLUSIONS: The p53 pathway is inactivated in most T1G3 bladder tumors. These genetic alterations do not independently predict patient's prognosis.	bladder
Postoperative thrombotic microangiopathy following radical cystectomy for bladder cancer.	This report describes the perioperative management of disseminated intravascular coagulation occurring abruptly during a planned cystectomy for non-metastatic bladder papillary carcinoma. Peroperatively, profuse bleeding and an acute decrease in blood pressure were effectively treated by blood transfusions and fresh frozen plasma. Haematological tests indicated the presence of disseminated intravascular coagulation. On the following three days, acute renal failure, peripheral disseminated intravascular coagulation-related thrombocytopenia and haemolytic anemia with schistocytes were suggestive of thrombotic microangiopathy. Treatment by plasma exchange along with haemodialysis was commenced. An aetiological work-up remained negative. After 21 days of treatment, haemodialysis and plasma exchange were stopped. Urological outcome was favourable. The one-year follow-up did not show any residual renal insufficiency and laboratory parameters returned to normal. In the absence of evidence in favour of an infectious, drug-related or immunological aetiology, we postulated that this thrombotic microangiopathy was caused by disseminated intravascular coagulation and that the tumour manipulation during the surgical procedure was the triggering factor.	bladder
Paraneoplastic production of granulocyte colony-stimulating factor in a bladder carcinoma.	We report the case of a 51-year-old female with poorly differentiated bladder carcinoma who presented with leukocytosis and hypercalcemia. Granulocyte colony-stimulating factor was noted to be twice the normal level. Paraneoplastic leukocytosis in bladder carcinoma is rare, is often associated with paraneoplastic hypercalcemia, and appears to represent a particularly aggressive form of the disease.	bladder
Function-preserving surgery for urologic cancer.	Radical surgery that is intended to cure cancer disease tends to cause some damage to the operated organ and the quality of life of the patient. It is now a worldwide trend to preserve the function and minimize the operative damage to the patient, without compromising the oncological outcome. In urologic cancers, nephron-sparing surgery for kidney tumors, and nerve-sparing procedures in radical cystectomy and radical prostatectomy for retaining potency are now more frequently used for providing better quality of life after surgery. New constructive surgeries such as neobladder formation and nerve graft techniques after complete removal of the cavernous nerve have been developed for recovering the lost function.	bladder